Pain is a symptom of many clinical disorders, which afflict a large population of humans, and is treated largely by a variety of pharmacological agents. Although most rapid changes and interesting findings in pain research are obtained in rodent species, it is not clear to what extent they can be replicated and applied to primate species. Humans and monkeys have similar thresholds for detecting noxious stimuli and the neural systems responsible for these sensations in the two species are fundamentally similar. Therefore, it is important to conduct monkey studies for characterizing novel experimental compounds, which have been proposed as better analgesics with less side effects in rodents. Both the warm water tail-withdrawal assay and respiration assay have been used to characterize the behavioral effects of various opioid compounds in monkeys. Both assays serve as valid in vivo endpoints for studying the efficacy and selectivity of opioid agonists and the characteristics of opioid antagonists. These assays will be employed during this grant period. In addition, we have established a new experimental pain model (i.e, capsaicin-induced thermal nociception) and an experimental itch model (i.e., central mu opioid receptor-mediated pruritus). These assays facilitate investigating the selective function of opioid receptor types and the sites of action of various opioids in primates. In addition, we have established intrathecal and Intracisternal injection techniques in monkeys, which have provided a valuable opportunity to enhance the pharmacological evaluation of opioids and pain in primates. This series of proposed studies has several aims including developing inflammatory pain models, studying the receptor systems involved in the pain processing, and evaluating distinct opioid agonists and antagonists. These studies will clarify the sites of action and effectiveness of novel analgesics and elucidate the therapeutic potential of experimental agents. The studies, taken together, will make a notable advance in our understanding of pain and analgesia and make a substantial contribution to pain research in primates.